Title:Isocitrate Lyase: A Potential Target for Anti-Tubercular Drugs
VOLUME: 7 ISSUE: 2
Author(s):Rohit Sharma, Oisik Das, Satyawan G. Damle and Anil K. Sharma
Affiliation:Department of Biotechnology, MMEC, M. M. University, Mullana-Ambala-133207.
Keywords:Isocitrate lyase, Mycobacterium tuberculosis, inhibition, persistence.
Abstract:Current TB regimen involves a combination of first and second line drugs which target only a small number of
core metabolic processes such as deoxyribonucleic acid (DNA)/ ribonucleic acid (RNA) synthesis, cell wall synthesis, and
energy metabolism pathways. New classes of drugs with additional drug targets that are resistant to mutation are an urgent
necessity. Novel targets involved in vital aspects of bacterial growth, metabolism and viability and whose inactivation
would lead to bacterial death or an inability to persist need to be investigated. Isocitrate lyase (ICL), which catalyses the
first step in the glyoxylate cycle is found to play a pivotal role in persistence of Mycobacterium tuberculosis in mice, can
be a potential target for anti-tubercular drug. The current review provides a detailed overview of the therapeutic potential,
patents and recent advancements in the investigative studies done on isocitrate lyase (ICL) as an antitubercular drug target.
Salicylanilide, benzanilide, 3-nitropropionamide and pthalazinyl derivatives, Pyruvate-isoniazid analogs and its copper complexes
are among the synthesized compounds showing a great potential to inhibit mycobacterial ICL and a significant antimycobacterial
effect. Some of the relevant patents in the ICL research have been further reviewed and discussed.